. .. This is a new investigator's revised application in response to PA-06-438, "Research on the Reduction and Prevention of Suicidality." There is an urgent need to address the growing public health problem of poisoning fatalities in the US. In 2003, there were 28,700 fatal poisonings and 817,797 non-fatal poisonings n the US. Opioid-related overdoses (ORO) are increasing at an alarming rate in portions of the US, especially ORO of unintentional and undetermined intent. The extent of misclassification of ORO (e.g., true suicides misclassified as unintentional deaths) is largely unknown, but recent findings that elevated depressive symptoms are associated with unintentional ORO raises concern. Much of the recent scientific literature is based on studies focused exclusively on intravenous heroin users conducted in Europe and Australia. Increasing misuse of prescription opioids in the US may limit the generalizability of these findings. The overall goals of this proposal are to identify factors associated with ORO and extend our knowledge of intentionality. Specific aims include: 1) identify distinguishing characteristics of intentional (suicidal) versus unintentional (accidental) ORO; 2) determine proximal and distal risk factors for ORO; and 3) develop and pilot a brief intent scale. This proposal is unique in that it: a) employs standardized suicide assessments; b) applies a case-crossover design to identify proximal risk factors for severe ("near miss") ORO, as defined by a biological marker (naloxone); and c) utilizes a cross-sectional cohort design to examine distal risk factors for ORO. A sample of 500 subjects recruited from five populations including an emergency department, detoxification center, methadone maintenance program, pain clinic, and the community will be used to test two hypotheses. Hypothesis I: Subjects with intentional ORO, compared to those with unintentional ORO, will have more depressive symptoms, but less apathy and less polydrug use. Hypothesis II: Depressive symptoms, long-acting prescription opioids and acute life events will trigger ORO. We will also explore a continuum of intent and impulsivity, prior ORO, risk-taking and hopelessness as distal risk factors for ORO. Public Health Significance: Results from these studies may enhance ORO risk-identification, provide methodological advances applicable to other areas of injury research, spur development of intervention strategies, and improve the quality of poisoning and suicide surveillance. [unreadable] [unreadable] [unreadable]